Table_3_Comparison of differential metabolites in brain tissue of aged marmosets and serum of elderly patients after prolonged anesthesia.docx

ObjectiveTo compare the differential metabolites in the brain tissue of aged marmosets after long-term anesthesia (≥ 6 h) and the serum of elderly patients by metabolomics methods.
MethodsSix aged marmosets (≥ 8 years old) were divided into two groups: anesthesia and control. The aged monkeys in the anesthesia group were induced with 6–8% sevoflurane and 100% oxygen (2 l/min) for 1–2 min and maintained with 1.5–2.5% sevoflurane and 100% oxygen (2 l/min) for 6 h. In the control group (n = 3), anesthesia was only induced under the same conditions for 1–2 min. The prefrontal cortex tissues of the two groups of aged marmosets were collected for metabolomics detection. Twenty-nine elderly patients (≥ 65 years old) who had undergone surgical anesthesia for more than 6 h were enrolled. Serum samples were collected before and on the first day after surgery for metabolomics analysis. Differential metabolites were compared between human serum and marmoset brain tissue.
ResultsThe changes in lactate and xanthurenic acid in the serum of elderly patients were consistent with those in the brain tissue of aged marmoset monkeys, that is, lactate was up-regulated and xanthurenic acid was down-regulated. However, serum levels of 5-methylterahydrofolic acid and leucine were down-regulated in elderly patients after anesthesia. In contrast, 5-methylterahydrofolic acid and leucine levels were up-regulated in the prefrontal cortex of aged marmosets compared with control marmosets. Furthermore, glycolysis/gluconeogenesis and pentose phosphate pathway were both significantly enriched in the prefrontal cortex of aged marmosets and serum of elderly patients after surgery.
ConclusionThe changes of serum metabolites in elderly patients are not exactly the same as the metabolic changes of brain tissues in aged marmosets. The metabolic changes in serum lactate and xanthurenic acid levels can reflect brain tissue metabolism. The enrichment pathways of differential metabolites in the serum of elderly patients and the brain tissue of aged marmosets were partially the same.

研究目的：通过代谢组学方法，比较长期麻醉（时长≥6小时）后的老年狨猴脑组织与老年患者血清中的差异代谢物。
研究方法：选取6只年龄≥8岁的老年狨猴，分为麻醉组与对照组。麻醉组老年狨猴采用6%~8%七氟烷（sevoflurane）联合100%氧气（流量2 L/min）诱导麻醉1~2分钟，随后以1.5%~2.5%七氟烷联合100%氧气（流量2 L/min）维持麻醉6小时。对照组（n=3）仅在相同实验条件下进行1~2分钟的麻醉诱导。采集两组老年狨猴的前额叶皮层（prefrontal cortex）组织进行代谢组学检测。招募29名年龄≥65岁、接受手术麻醉时长超过6小时的老年患者，分别于术前及术后首日采集血清样本开展代谢组学分析，比较人类血清与狨猴脑组织中的差异代谢物。
研究结果：老年患者血清中乳酸与犬尿喹啉酸（xanthurenic acid）的变化趋势与老年狨猴脑组织一致，即乳酸水平上调、犬尿喹啉酸水平下调。但老年患者麻醉后血清中5-甲基四氢叶酸（5-methylterahydrofolic acid）与亮氨酸水平呈下调趋势；与之相反，相较于对照组狨猴，麻醉组老年狨猴前额叶皮层中的5-甲基四氢叶酸与亮氨酸水平则显著上调。此外，糖酵解/糖异生途径与磷酸戊糖途径在老年狨猴前额叶皮层及术后老年患者血清中均显著富集。
结论：老年患者血清代谢物的变化与老年狨猴脑组织的代谢变化并非完全一致。血清乳酸与犬尿喹啉酸水平的变化可反映脑组织代谢状态；老年患者血清与老年狨猴脑组织中差异代谢物的富集通路存在部分重合。